Complication after Aquafilling® gel-mediated augmentation mammoplasty—galactocele formation in a lactating woman: a case report and review of literature

Augmentation mammoplasty using hydrogel fillers such as polyacrylamide gel (PAAG) or Aquafilling® has been performed commonly in some countries as an alternative to breast augmentation with saline or silicone implants. However, the safety of this procedure remains controversial, and many complications associated with the use of large-volume hydrogel injection have been reported in recent years. We present the case of a 33-year-old woman with a history of bilateral Aquafilling® injection augmentation mammoplasty who presented with an enlarged left breast while breastfeeding. Based on the clinical presentation and ultrasound findings, the patient underwent surgical incision as abscess formation caused by infection of the filler material could not be ruled out with certainty. Surgery revealed a galactocele with drainage of large amounts of milky fluid. Remaining filler material was removed as thoroughly as possible, and vacuum assisted wound dressing was performed. Galactocele formation in lactating women is a known complication after injection of hydrogel. Hence, it is important to be familiar with this uncommon but possibly severe complication in order to make an accurate diagnosis and initiate adequate treatment. To that end, it is recommended that patients who underwent Aquafilling® injection for breast augmentation should avoid lactation and that women intending to breastfeed should not undergo augmentation mammoplasty with injection of Aquafilling®.Level of Evidence: Level V, risk / prognostic stud

Single-incision for breast-conserving surgery through round block technique

Aims and objectives: The purpose of this study was to assess the feasibility of using the single-incision round block technique in breast-conserving surgery with sentinel lymph node (SLN) retrieval for breast cancer without compromising oncological safety. Materials and methods: A retrospective observational case-control study was conducted from January 2017 to October 2021. The study population consisted of two groups. In both groups, breast-conserving surgery was carried out through the round-block technique. In group A, SLN retrieval was performed using the round-block incision (study group), while in group B, SLN retrieval was conducted through a second skin incision in the axilla (control group). The study was approved by the local ethics committee Zurich (BASEC-Nr. 2020-02857), and written informed consent was obtained from all participants. Results: Overall, 134 patients met the inclusion criteria, of whom 86 women underwent breast-conserving surgery and SLN retrieval using the single-incision approach (group A), and 48 women underwent conventional surgery, using two independent incisions for tumour resection and SLN retrieval (group B). The overall success rate in group A regarding SLN retrieval was 97.7%, whereas most tumours were located in the upper outer (47.7%) and upper inner quadrant (27.9%). Although the technique was equally successful in the other quadrants, the share of tumours in the lower outer, and the lower inner quadrant, and the retroareolar region was smaller, representing 17.4%, 3.5% and 3.5%, respectively. The median number of dissected lymph nodes was two, with a positivity rate of 24.4%. The occurrence of axillary neuralgia and axillary skin retraction was significantly higher in group B along with tendentially more axillary seroma formation. There were no significant differences regarding reintervention rates, in terms of complications, resection margins, locoregional recurrences, or deaths with a mean follow-up of 11 months. Conclusions: The single-incision method through the round block technique is as safe and effective as the standard two-incision approach regarding nodal staging and resection margins, and seems to be applicable for tumours in all breast quadrants. Keywords: Benelli; Breast-conserving surgery; Minimal-access breast surgery; Round block; Single-incision

Border Insecurity: Reading Transnational Environments in Jim Lynch’s Border Songs

This article applies an eco-critical approach to contemporary American fiction about the Canada-US border, examining Jim Lynch’s portrayal of the British Columbia-Washington borderlands in his 2009 novel Border Songs. It argues that studying transnational environmental actors in border texts—in this case, marijuana, human migrants, and migratory birds—helps illuminate the contingency of political boundaries, problems of scale, and discourses of risk and security in cross-border regions after 9/11. Further, it suggests that widening the analysis of trans-border activity to include environmental phenomena productively troubles concepts of nature and regional belonging in an era of climate change and economic globalization. Cet article propose une lecture écocritique de la fiction étatsunienne contemporaine portant sur la frontière entre le Canada et les États-Unis, en étudiant le portrait donné par Jim Lynch de la région frontalière entre la Colombie-Britannique et Washington dans son roman Border Songs, paru en 2009. L’article soutient que l’étude, dans les textes sur la frontière, des acteurs environnementaux transnationaux – dans ce cas-ci, la marijuana, les migrants humains et les oiseaux migratoires – jette un jour nouveau sur la contingence des limites territoriales politiques, des problèmes d’échelle et des discours sur le risque et la sécurité des régions transfrontalières après les évènements du 11 septembre 2001. Il suggère également qu’en élargissant l’analyse de l’activité transfrontalière pour y inclure les phénomènes environnementaux, on brouille de façon productive les concepts de nature et d’appartenance régionale d’une époque marquée par les changements climatiques et la mondialisation de l’économie

Brain volumetric deficits in MAPT mutation carriers: a multisite study

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volume

Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration

Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression. Methods: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. Results: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. Conclusions: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. Trial registration information: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. Classification of evidence: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Effect of a Dwell Stage in the Cure Cycle on the Interphase Formation in a Poly(ether imide)/High T_gEpoxy System

Epoxies are inherently brittle materials and to overcome this brittleness, a second microphase (i.e., thermoplastic) is typically added. This modification of epoxy resin using thermoplastics results in reaction-induced phase separating morphologies in the micrometer range. In this study, the influence of the curing history, beyond phase separation, on the interphase formation and final morphology of PEI and the high Tg epoxy system is investigated. Several cure cycles were examined, each with a first dwell temperature ranging from 120 to 180 °C for a given time up to the onset of phase separation (OPS) or up to the 80% degree of cure (80% DOC) and then with a second dwell at 200 °C for 20 min to complete the cure cycle. Hot-stage microscopy experiments were carried out at several first dwell temperatures before final conversion at the second dwell. The morphologies and resulting droplet size distribution at the interphase, after the final cure, were analyzed through scanning electron microscopy. Results showed that the diffusion distance was significantly higher in the case of OPS as compared to the 80% DOC case, particularly at lower first dwell temperatures. This behavior was attributed to the fact that, in the case of OPS, polymeric chains were still in a mobile state and diffused further during the second dwell curing stage, while at 80% DOC, polymeric chains were completely bound but still diffuse due to non-stoichiometric curing. This restricted mobility of polymeric chains after phase separation (80% DOC) resulted in a larger number of smaller droplets as compared to the OPS case.Aerospace Manufacturing Technologie

FASN Inhibition and Taxane Treatment Combine to Enhance Anti-tumor Efficacy in Diverse Xenograft Tumor Models through Disruption of Tubulin Palmitoylation and Microtubule Organization and FASN Inhibition-Mediated Effects on Oncogenic Signaling and Gene Expression

Palmitate, the enzymatic product of FASN, and palmitate-derived lipids support cell metabolism, membrane architecture, protein localization, and intracellular signaling. Tubulins are among many proteins that are modified post-translationally by acylation with palmitate. We show that FASN inhibition with TVB-3166 or TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression. Disrupted microtubule organization in tumor cells is an additional consequence of FASN inhibition. FASN inhibition combined with taxane treatment enhances inhibition of in vitro tumor cell growth compared to treatment with either agent alone. In lung, ovarian, prostate, and pancreatic tumor xenograft studies, FASN inhibition and paclitaxel or docetaxel combine to inhibit xenograft tumor growth with significantly enhanced anti-tumor activity. Tumor regression was observed in 3 of 6 tumor xenograft models. FASN inhibition does not affect cellular taxane concentration in vitro. Our data suggest a mechanism of enhanced anti-tumor activity of the FASN and taxane drug combination that includes inhibition of tubulin palmitoylation and disruption of microtubule organization in tumor cells, as well as a sensitization of tumor cells to FASN inhibition-mediated effects that include gene expression changes and inhibition of β-catenin. Together, the results strongly support investigation of combined FASN inhibition and taxane treatment as a therapy for a variety of human cancers

Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling Pathways, and Reprogramming Gene Expression

Inhibition of de novo palmitate synthesis via fatty acid synthase (FASN) inhibition provides an unproven approach to cancer therapy with a strong biological rationale. FASN expression increases with tumor progression and associates with chemoresistance, tumor metastasis, and diminished patient survival in numerous tumor types. TVB-3166, an orally-available, reversible, potent, and selective FASN inhibitor induces apoptosis, inhibits anchorage-independent cell growth under lipid-rich conditions, and inhibits in-vivo xenograft tumor growth. Dose-dependent effects are observed between 20–200 nM TVB-3166, which agrees with the IC50 in biochemical FASN and cellular palmitate synthesis assays. Mechanistic studies show that FASN inhibition disrupts lipid raft architecture, inhibits biological pathways such as lipid biosynthesis, PI3K–AKT–mTOR and β-catenin signal transduction, and inhibits expression of oncogenic effectors such as c-Myc; effects that are tumor-cell specific. Our results demonstrate that FASN inhibition has anti-tumor activities in biologically diverse preclinical tumor models and provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers, including those expressing mutant K-Ras, ErbB2, c-Met, and PTEN. The reported findings inform ongoing studies to link mechanisms of action with defined tumor types and advance the discovery of biomarkers supporting development of FASN inhibitors as cancer therapeutics. Research in context: Fatty acid synthase (FASN) is a vital enzyme in tumor cell biology; the over-expression of FASN is associated with diminished patient prognosis and resistance to many cancer therapies. Our data demonstrate that selective and potent FASN inhibition with TVB-3166 leads to selective death of tumor cells, without significant effect on normal cells, and inhibits in vivo xenograft tumor growth at well-tolerated doses. Candidate biomarkers for selecting tumors highly sensitive to FASN inhibition are identified. These preclinical data provide mechanistic and pharmacologic evidence that FASN inhibition presents a promising therapeutic strategy for treating a variety of cancers